Using extracellular single unit recording techniques we have found that sulfated cholecystokinin (CCK) octapeptide when administered either systemically or iontophoretically potentiates the actions of dopamine (DA) on DA autoreceptors in the mesolimbic DA system. Furthermore, we found that all varieties of CCK-like peptides which bind to brain CCK receptors also potentiate DA in the ventral tegmental area (VTA) and medial substantia nigra (SN), but that those CCK-like peptides which do not bind to brain CCK receptor sites were ineffective in potentiating DA. We have also found that the putative CCK antagonists, proglumide and benzotript, weakly blocked CCK in proportion to their potency at central CCK receptors. The ability of CCK to potentiate DA only occurs in those midbrain regions where DA and CCK coexist. We have also found that the anxiogenic benzodiazepine (BZ) receptor ligand, beta-carboline carboxylate ethyl ester (BetaCCE) increases the activity of neurons in the SN zona reticulata but has no effect on noradrenergic neurons in the locus coeruleus. Caffeine also mimics many of the effects of BetaCCE in the SN but its actions are not reversed by the specific BZ antagonist Ro-15-1788 as are those of BetaCCE. It appears that the substantia nigra zona reticulata is sensitive to the effects of anxiolytic and anxiogenic compounds, as well as anticonvulsant and proconvulsant drugs.